Mitochondria-Rich Extracellular Vesicles from Bone Marrow Stem Cells Mitigate Muscle Degeneration in Rotator Cuff Tears in a Rat Model through Macrophage M2 Phenotype Conversion.
Xing Gao, Yuanyuan Chen, Jingzeng Wang, Jian Xu, Hu Wan, Xiao Li, Yulong Shi
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引用次数: 0
Abstract
Purpose: This study aimed to investigate the protective effects of extracellular vesicles derived from bone marrow stem cells (BMSC-EVs) on muscle degeneration in a rat model of rotator cuff tendon and suprascapular nerve (SSN) transection (termed the RCT-SSN model), focusing on mitochondrial transfer.
Methods: The EVs were identified and characterized. RCT-SSN model was established by transecting the supraspinatus, infraspinatus tendons, and suprascapular nerve. Ninety-six rats were divided into four groups (n=24 each): sham surgery, RCT-SSN treated with BMSC-EVs, RCT-SSN treated with EVs from Rhodamine-6G-pretreated BMSCs (Rho-EVs), or phosphate-buffered saline (PBS). Intramuscular injections were administered every two weeks. After 12 weeks, supraspinatus muscles were analyzed for atrophy, fibrosis, oxidative stress, macrophage phenotypes, serum cytokines, and mitochondrial characteristics. In vitro experiments included EVs tracking in macrophages, macrophage phenotype characterization, and inflammatory cytokine profiling.
Results: BMSC-EVs and Rho-EVs displayed similar morphology, but only BMSC-EVs contained functional mitochondria. BMSC-EVs significantly reduced muscle weight loss (0.047 ± 0.010% vs. 0.145 ± 0.013%, P < 0.001), increased muscle fiber cross-sectional area (2037 ± 231.9 μm2 vs. 527.9 ± 92.01 μm2, P < 0.001), and decreased fibrosis (12.09 ± 3.31% vs. 25.69 ± 4.84%, P < 0.001) compared to PBS. BMSC-EVs enhanced superoxide dismutase activity (93.3 ± 11.8 U/mg protein vs. 53.4 ± 8.0 U/mg protein, P < 0.001), improved mitochondrial function, density and structure, and induced an anti-inflammatory macrophage shift, suppressing proinflammatory cytokines in vitro and in vivo. Rho-EVs showed no such effects.
Conclusions: This study showed that transecting the supraspinatus, infraspinatus tendons, and suprascapular nerve in a rat model induced muscle degeneration and fibrosis. BMSC-EVs, but not Rho-EVs, mitigated these effects by promoting an anti-inflammatory macrophage phenotype and protecting mitochondrial function through mitochondrial transfer.
Clinical relevance: Mitochondrial transfer via BMSC-EVs may offer a therapeutic strategy to prevent muscle degeneration in rotator cuff tear patients.
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Nowhere is minimally invasive surgery explained better than in Arthroscopy, the leading peer-reviewed journal in the field. Every issue enables you to put into perspective the usefulness of the various emerging arthroscopic techniques. The advantages and disadvantages of these methods -- along with their applications in various situations -- are discussed in relation to their efficiency, efficacy and cost benefit. As a special incentive, paid subscribers also receive access to the journal expanded website.
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